+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-24402 | |||||||||
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タイトル | SARS-CoV-2 Spike in complex with PVI.V6-14 Fab | |||||||||
マップデータ | Locally refined, sharpened map of SARS-CoV-2 Spike NTD in complex with PVI.V6-14 | |||||||||
試料 |
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キーワード | virus / neutralizing antibody / vaccine / plasmablast / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | 機能・相同性情報 Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / immune response / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / extracellular space / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) / Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.7 Å | |||||||||
データ登録者 | Altomare CG / Bajic G | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: mBio / 年: 2022 タイトル: Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain. 著者: Clara G Altomare / Daniel C Adelsberg / Juan Manuel Carreno / Iden A Sapse / Fatima Amanat / Ali H Ellebedy / Viviana Simon / Florian Krammer / Goran Bajic / 要旨: Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs ...Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy complementarity-determining region 3 (HCDR3) loop into a hydrophobic NTD cavity previously shown to bind a heme metabolite, biliverdin. We demonstrate direct competition with biliverdin and that, because of the conserved nature of the epitope, the mAb maintains binding to viral variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Our study describes a novel conserved epitope on the NTD that is readily targeted by vaccine-induced antibody responses. We report the first structure of a vaccine-induced antibody to SARS-CoV-2 spike isolated from plasmablasts 7 days after vaccination. The genetic sequence of the antibody PVI.V6-14 suggests that it is completely unmutated, meaning that this type of B cell did not undergo somatic hypermutation or affinity maturation; this cell was likely already present in the donor and was activated by the vaccine. This is, to our knowledge, also the first structure of an unmutated antibody in complex with its cognate antigen. PVI.V6-14 binds a novel, conserved epitope on the N-terminal domain (NTD) and neutralizes the original viral strain. PVI.V6-14 also binds the newly emerged variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Given that this antibody was likely already present in the donor prior to vaccination, we believe that this antibody class could potentially "keep up" with the new variants, should they continue to emerge, by undergoing somatic hypermutation and affinity maturation. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_24402.map.gz | 902.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-24402-v30.xml emd-24402.xml | 15.2 KB 15.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_24402_fsc.xml | 21.6 KB | 表示 | FSCデータファイル |
画像 | emd_24402.png | 25.9 KB | ||
Filedesc metadata | emd-24402.cif.gz | 5.8 KB | ||
その他 | emd_24402_additional_1.map.gz | 512.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-24402 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24402 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_24402_validation.pdf.gz | 335.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_24402_full_validation.pdf.gz | 334.9 KB | 表示 | |
XML形式データ | emd_24402_validation.xml.gz | 19 KB | 表示 | |
CIF形式データ | emd_24402_validation.cif.gz | 26.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24402 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24402 | HTTPS FTP |
-関連構造データ
関連構造データ | 7rbuMC 7rbvC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
電子顕微鏡画像生データ | EMPIAR-11127 (タイトル: Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain Data size: 5.1 TB Data #1: Unaligned multi-frame movies of SARS-CoV-2 spike glycoprotein in complex with PVI.V6-14 Fab [micrographs - multiframe]) |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_24402.map.gz / 形式: CCP4 / 大きさ: 1 GB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Locally refined, sharpened map of SARS-CoV-2 Spike NTD in complex with PVI.V6-14 | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.56 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: Locally refined, unsharpened map of SARS-CoV-2 Spike NTD...
ファイル | emd_24402_additional_1.map | ||||||||||||
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注釈 | Locally refined, unsharpened map of SARS-CoV-2 Spike NTD in complex with PVI.V6-14 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : SARS-CoV-2 Spike:PVI.V6-14 Fab complex
全体 | 名称: SARS-CoV-2 Spike:PVI.V6-14 Fab complex |
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要素 |
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-超分子 #1: SARS-CoV-2 Spike:PVI.V6-14 Fab complex
超分子 | 名称: SARS-CoV-2 Spike:PVI.V6-14 Fab complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
分子量 | 理論値: 550 kDa/nm |
-分子 #1: Spike protein S1
分子 | 名称: Spike protein S1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
分子量 | 理論値: 33.417703 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG ...文字列: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LVRDLPQGFS ALEPLVDLPI GINITRFQTL LALHRSYLTP GD SSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFT UniProtKB: Spike glycoprotein |
-分子 #2: PVI.V6-14 Fab heavy chain, variable region
分子 | 名称: PVI.V6-14 Fab heavy chain, variable region / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 13.932396 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: QVQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY YNPSLKSRVT ISVDTSKNQF SLKLSSVTA ADTAVYYCAR CRPEYYFGSG SYLDFDYWGQ GTLVTVSS |
-分子 #3: PVI.V6-14 Fab light chain, variable region
分子 | 名称: PVI.V6-14 Fab light chain, variable region / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 11.385669 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: DIQMTQSPSS VSASVGDRVT ITCRASQGIS SWLAWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ QANSFPLTFG GGTKVEIK UniProtKB: IGL c1310_light_IGKV1-12_IGKJ4 |
-分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 5 / コピー数: 3 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 1 mg/mL |
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緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |